Long non-coding RNA (lncRNA) is emerging as an essential player in cancer progression. However, its biological function and clinical implication in papillary thyroid carcinoma (PTC) remain poorly understood. In the current study, we found that a novel lncRNA, ASMTL antisense RNA 1 (ASMTL-AS1), was significantly downregulated in PTC. And its downregulation was positively linked to larger tumor size, advanced clinical stage and unfavorable outcome. Overexpression of ASMTL-AS1 evidently inhibited PTC cell proliferation and glycolysis, while knockdown of ASMTL-AS1 resulted in the opposite effect. Regarding the mechanism, ASMTL-AS1 was capable of sponging miR-93-3p and miR-660 to elevate FOXO1 expression, leading to repressing glycolysis and tumorigenesis. In turn, FOXO1 could also increase ASMTL-AS1 expression via directly binding to ASMTL-AS1 promoter, which formed a positive feedback regulation loop. Importantly, the regulatory axis of ASMTL-AS1/miR-93-3p/miR-660/FOXO1 was also identified in vivo. Collectively, our data clearly indicate that ASMTL-AS1 functions as a novel tumor suppressor in PTC through regulation of miR-93-3p/miR-660/FOXO1 pathway. Targeting ASMTL-AS1 and its downstream pathway may be an effective therapeutic approach for patients with PTC.

中文翻译：

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较长的非编码RNA ASMTL-AS1通过调节甲状腺乳头状癌中的miR-93-3p / miR-660 / FOXO1轴来抑制肿瘤生长和糖酵解。

长非编码RNA（lncRNA）逐渐成为癌症进展中的重要角色。然而，其生物学功能和在甲状腺乳头状癌（PTC）中的临床意义仍然知之甚少。在当前的研究中，我们发现PTC中显着下调了新型lncRNA ASMTL反义RNA 1（ASMTL-AS1）。而且其下调与更大的肿瘤大小，晚期临床分期和不良预后呈正相关。ASMTL-AS1的过表达明显抑制了PTC细胞的增殖和糖酵解，而敲低ASMTL-AS1则产生了相反的作用。关于机制，ASMTL-AS1能够使miR-93-3p和miR-660海绵化，从而提高FOXO1的表达，从而抑制糖酵解和肿瘤发生。反过来，FOXO1还可以通过直接与ASMTL-AS1启动子结合而增加ASMTL-AS1表达，从而形成一个正反馈调节环。重要的是，还在体内鉴定了ASMTL-AS1 / miR-93-3p / miR-660 / FOXO1的调节轴。总体而言，我们的数据清楚地表明，通过调节miR-93-3p / miR-660 / FOXO1途径，ASMTL-AS1在PTC中起着新型的抑癌作用。靶向ASMTL-AS1及其下游途径可能是PTC患者的有效治疗方法。